The field of this invention is extended pain relief methods and compositions.
The mechanism of pain generation in post-herpetic neuralgia is unknown. Post-herpetic neuralgia (PHN) begins with a cutaneous rash and the chronic state is notable for skin scarring and painfully sensitive skin (allodynia). Although the initial outbreak may be widespread, occasionally appearing to cover more than the area of skin innervated by a single dorsal root ganglion, most PHN patients are able to localize a limited area of skin as the source of their pain. PHN patients nearly always have a sensory deficit in the region obtained.
The majority of work carried out on topical agents for analgesia in recent years has been in patients with PHN. Other conditions, particularly diabetic neuropathy, have been treated in clinical trials and clinical practice with topical agents, primarily capsaicin. Topical therapies represent a very attractive alternative to oral medications for conditions like PHN. The primarily elderly patients with PHN frequently cannot be treated with tricyclic antidepressants because of pre-existing cognitive impairment, cardiac disease, or systemic illness. Diabetic autonomic disfunction may significantly enhance orthostatic hypotension from tricyclic antidepressants. Side effects like constipation, dry mouth and sedation may prove so bothersome that compliance becomes a major problem in therapy. Anticonvulsants are of uncertain efficacy in PHN, though carbamazepine and antiarrhythmics like mexiletine are effective for diabetic neuropathy. Non-narcotic analgesics are rarely effective and benzodiazepines have been proven ineffective. Opioids may be effective, but have not been adequately evaluated as long term treatment for PHN or diabetic neuropathy.
The use of local anesthetics to control the pain of herpes-zoster PHN has a history dating back to Wood""s 1929 report of complete relief of ophthalmic PHN from injection of procaine into the supraorbital nerve (Wood, Am. J. Ophthalmol. (1929) 12: 759-760). Since that time, local anesthetics have been given to millions of patients by the epidural route, intravenously, as stellate ganglion blocks, as peripheral nerve and intercostal nerve blocks, and by nearly every other conceivable route to control the pain of acute zoster and PHN. Once PHN is well established, local anesthetic peripheral nerve, epidural, or synthetic blocks are unlikely to provide more than temporary relief. For such a chronic condition, it is difficult to justify highly invasive procedures, with substantial risks, just to gain hours, or at best days, of relief.
There is, therefore, substantial interest in being able to devise simple procedures which will allow for long term relief from the pain associated with herpes-zoster or PHN. Desirably, such relief should have a simple protocol, so as to minimize the continued monitoring by the patient of the treatment for pain relief. By providing for simple, easily performed protocols which do not require short term repetitive administration, elderly patients can self-administer their treatment without concerns as to adverse effects resulting from maladministration.
Relevant Literature
The following are representative of the medical literature pertaining to management of postherpetic neuralgia and herpes zoster:
Colding. A., Proc. R. Soc. Med. (1971) 66: 541-543, describes the use of local anesthetics to treat herpetic pain.
Dan, K et al., 9 Advances in Pain Research and Therapy (eds. Field et al.) (1985), pp. 831-838, describe the use of nerve block to treat herpetic pain.
Hallen, B. et al., Anesthesiology (1982) 57: 340-342, describe the use of lidocaine-prilocaine cream to reduce the pain associated with bladder catheter insertion.
Hanks and White, Br. Med. J. (1988) 297: 1215, describes local anaesthetic creams.
King, R. B., Pain (1988) 33: 73-78, describes the use of an aspirin/chloroform mixture to treat post-herpetic neuralgia and herpes zoster.
Kissin et al., Neurology (1989) 39: 1132, describes the use of topical lidocaine for relief of superficial pain in postherpetic neuralgia.
Luben, N. M. et al., Am. J. Dis. Child. (1974) 128: 92-194, describe the use of a 30% lidocaine patch for anesthesia in minor surgery.
Milligan et al., Br. Med. J. (1989) 298: 253, describe the use of a lignocaine-prilocaine cream in an anecdotal treatment of postherpetic neuralgia.
Mollgaard, B. and Hoelgaard, A., Acta. Pharm. Suec. (1983) 20:43-450 describe drug permeation formulations.
Reiz, G. M. E. E. and Reiz, S. L. A., Acta. Anaesth. Scand. (1982) 26:596-598, describe a topical anaesthetic compound.
Rowbotham and Fields, Pain (1989) 38: 297-301, describe the reduction in the pain of PHN with a topical lidocaine application.
Rowbotham, M. C., Herpes Zoster and Postherpetic Neuralgia (ed. Watson) (1993) pp. 185-203.
Russo. J. et al., Am. J. Hosp. Pharm. (1980) 37: 843-847, compare the effectiveness of different methods of lidocaine administration.
Sarpotdar, P. and Zatz, J., J. Pharm. Sciences. (1986) 75: 176-18, describe the penetration enhancement through hairless mouse skin of lidocaine by nonionic surfactants.
Secunda, L. et al., N. Engl. J. Med. (1941) 224: 501-503, describe the treatment of herpetic pain through cutaneous infiltration of local anesthetics.
Stow et al., Pain (1989) 39:301-305, describe the pharmacokinetics and efficacy of treating PHN with an EMLA cream.
Watson, C. P. et al., Neurology (1982) 32: 671-673, describe the use of amitriptyline for treatment of postherpetic neuralgia.
Methods and compositions are provided for safely reducing nerve injury pain from shingles (herpes zoster and post herpetic neuralgia) and analogous neuropathies. The methods employ lidocaine intradermal administration by transport from the skin surface for a predetermined period, whereby the lidocaine is at a dosage below that which induces anesthesia and harmful systemic side effects, during at least a substantial portion of the period of administration. The administration may be terminated, whereby extended relief is frequently obtained subsequent to the termination of the administration. Particularly, patches and dressings are employed, where the lidocaine is formulated to provide for transport of the lidocaine into the skin for a predetermined time period.